The development of the domestic cat as an animal model for genetic analysis began with the construction of a genetic map which now consists of over 50 loci. A striking linkage homology of the human and feline gene maps was confirmed by cytological procedures and today over 25% of the human genome can be aligned band for band with the feline karyotype. Typing sera for the feline major histocompatibility complex were generated by allogenic skin grafting and serological reagents were evaluated by population cluster analysis and by immunoprecipitation of feline lymphocyte antigens. The molecular organization of the feline MHC complex was derived using homologous gene clones and compared to the human and murine MHC clusters. Evolution of the proto-oncogene family of mammals has been studied by mapping these genes in cat, mouse and man, and reconstructing their natural history. Two endogenous retroviral families (RD-114 and FeLV) have been studied from a molecular perspective and appear to represent vestiges of ancient infections and gene amplification in the Felidae. An evolutionary tree of 37 species of the cat family has been constructed using two molecular measures of genetic distance.